FI104051B - Inhaleringanordning - Google Patents

Description

104051

The present invention relates to an inhaler for use with an aerosol can comprising a body and a discharge spindle movable relative to the body-5 from a resting position prevented from being discharged to an operating position where the body is provided with an inhalation device. via a patient inhaling, both an inhibitory and pressure-responsive member having a first position to prevent relative movement between the release spindle and the body to an operating position, and a second position 10 to allow such movement, wherein said member recognizes a reduced inhalation produced by the patient the pressure and in return moves from the first position to the second position. In particular, the present invention relates to a metered dose inhaler which allows a certain amount of a drug-containing fluid to be delivered to a patient as an aerosol.

15

Measurement inhalation devices are quite well known in the medical art for treating or relieving symptoms of respiratory problems, for example asthma. The drug-containing fluid is pressurized in a can, which is mounted, usually in a removable manner, on the inhaler. The aerosol can comprises a body and a discharge spindle movable with respect to the body from a non-deployed non-deployed position to a "" operating position; eruption. In order to operate the inhaler, the patient must achieve a relative movement between the aerosol can body and the discharge spindle, for example, by pressing the closed end of the body, whereby the patient must coordinate this • · * ·· * 25 inhalation. Unfortunately, many patients in need of this type of treatment are unable to coordinate their breathing with the manual movement of the device.

In order to overcome this problem, devices with inhalation • # · have been suggested. * 30 function causes the device to release a dose of medicine. Such devices are called breathing devices.

: "': When designing a respiratory inhaler, the entire I · t set of conditions must be met, but they are difficult to reconcile. to overcome this problem, it has been proposed to provide the inhaler with an auxiliary energy reservoir, for example in the form of a spring, whereby the spring tends to force the device itself to release the dose while at the same time blocking the device. The small force produced by the inhalation is then used to release the blocking mechanism, allowing the spring to operate the device.

However, this in turn brings with it the additional problem of maintaining the stability of the device. If the small force produced by the inhalation is able to release the barrier mechanism, there is a risk that it may also be accidentally released when the inhalation is not performed. Conversely, if the barrier mechanism is held in place with sufficient depth to prevent accidental discharge, the force that the patient is able to exert by inhalation may not be sufficient to trigger it.

It is an object of the present invention to provide an inhaler device which takes into account these conflicting requirements and provides a workable solution.

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* << «« ':: The device according to the invention is characterized in that said inhibitory and: .i .: pressure-sensitive member is elastic! a flexible plate extending from a first * * * 25 stationary position relative to the body and a second position integral to the body of the aerosol can, the disc flexing as it moves from its first position to the second position or vice versa.

* * * v * In a preferred embodiment of the invention, a member referred to as a blocking member or

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*. * '30, a barrier and pressure sensitive member, is an elastically flexible plate, for example: a metal such as steel. Alternatively, it is possible to use a pair of disks: / which do not need to be resiliently flexible and which disks are joined by a function · · ·. here's the hell. One possible way to accomplish this is to have a pair of disks ♦ * ·. ·. : and the hinge are the same piece, for example, so that the hinge is the • »3 104051“ living ”hinge. The same effect can be achieved by using a single plate which is thinner in the transverse line to such an extent that the portion of the smaller thickness actually forms the hinge axis.

Numerous embodiments of the invention will now be described with reference to the accompanying drawings, in which:

Figure 1 shows a first embodiment, and the figure is a vertical sectional view taken along line A-A in Figure 2; 10

Figure 2 shows a first embodiment, and the figure is a vertical section along line B-B in Figure 1;

Figure 3 is a cross-sectional view taken along line C-C in Figure 1; 15

Figure 4 illustrates another embodiment of the invention, and the figure is a vertical section along line B-B of Figure 5;

Figure 5 is a vertical sectional view taken along line B-B of Figure 4; 20

Figure 6 is a sectional view taken along line C-C in Figure 4; · ·

Fig. 7 is a top plan view of the embodiment of Figs. 4-6; Figure 8 shows a third embodiment of the invention, and the figure is a vertical section through the line A-A in Figure 9; • «· • · ·

Figure 9 is a vertical sectional view taken along line B-B of Figure 8; * I I> • · · · · · · ·. Figure 30 is a cross-sectional view taken along line C-C in Figure 8; Fig. 11 shows a fourth embodiment of the invention, and the Fig. Is a vertical sectional view in line A-A of Fig. 12;

Figure 12 is a sectional view taken along line B-B of Figure 11;

Figure 13 is a cross-sectional view taken along line C-C of Figure 12; Figure 14 corresponds to Figure 11 but shows the device in a different position;

Figure 15 illustrates a fifth embodiment of the invention, and the figure is a vertical section through line A-A of Figure 16; Figure 16 is a sectional view taken along line B-B of Figure 15;

Fig. 17 is a cross-sectional view taken along line C-C in Fig. 16;

Fig. 17a is a perspective view of the resilient pin 15 used in Figs. 15-17;

Figure 18 illustrates a sixth embodiment of the invention, and the figure is a vertical section through line A-A of Figure 19; Figure 19 is a sectional view taken along line B-B of Figure 18; Fig. 20 is a cross-sectional view taken along line C-C in Fig. 19; «I 4

Fig. 21 is a top plan view of a sixth embodiment and showing a reset position of the embodiment; and Fig. 22 is a partial side view of a sixth embodiment in the position shown in Fig. 21.

We now move to the first embodiment shown in FIGS. 1-3, comprising a diaper 2 provided with an outlet nozzle 4 made of the same piece. This is shown in the form of a mouthpiece, such as; sex will be called in the future, but could alternatively be in the form of a cam • tl; ··. · lyle. On the inside of the sheath 2 is a separate compartment 6, in which the body of the aerosol can 10104051 and 8 is placed. The compartment 6 is slightly longer than the body of the aerosol can, and the body can slide longitudinally in the compartment. The body comprises markings, for example in the form of colored stripes 10 and 12, which may be green or red, for example. Either of these stripes may be seen from the opening 14 in the front wall of the sheath 2 according to the respective longitudinal position of the aerosol can body.

The aerosol can has a discharge arm 16 which protrudes from the body portion in a conventional manner and terminates in an opening in a shaft member 18 formed of the same body as the mouthpiece 4. The opening is grooved at a point where the discharge arm protrudes to facilitate insertion of the discharge arm. The other end of the discharge arm is pressed against the shoulder 20 and the discharge arm outlet is communicating with the discharge port 22. As usual, the discharge arm is bevelled outwardly from the body with a spring (not shown).

15

The guide 24 can slide in the longitudinal direction in the compartment 6. As can be most clearly seen in Fig. 2, its general shape is H when viewed in the longitudinal section. The guide comprises a transverse wall 25. The upper end of the sheath 2 is closed by a cover 26, and a pressure 20 spring 28 is disposed between the transverse wall 25 of the guide 24 and the cover 26 to force the guide, and thus the body of the aerosol can. the lid can preferably be removed so that the empty can can be I «« '·; change to a new can.

«I •« «

A guide groove 30 is formed in the guide 24, and the spacer 18 has a '· * · *. 25 formed upward groove 32. The upper and lower edges of the resiliently resilient plate 34 are in contact with the groove 30 and 32, respectively. This plate may suitably be made of steel sheet a few hundred millimeters thick, although other materials could be used instead. In non-stressed condition, the disk 34 • · · is substantially level. In the position shown in Figures 1 to 3, hereinafter referred to as the tensioned position, the plate 34 is slightly curved and longitudinally forced from the center 36 by the force exerted by the spring 28 on the plate. The side edges of the plate 34 are close to the side walls 37 of the sheath 2, but with sufficient clearance under the plate for easy movement, as described above.

6 104051

The chamber 38 is a separate part between the plate 34 and the rear wall of the sheath 2. A keyhole-shaped cut is made in the back wall of the jacket to define a keyhole-shaped tab 40, respectively. The slit width is selected with a view to providing an appropriate airflow rate into chamber 5 to facilitate release of the dose of drug. The tongue is attached to the remainder of the wall at its lower end, and the material of the rear wall, at least at the tongue attachment point, is flexible enough to be pushed inward and resilient enough to bounce back into its original position when power is no longer applied. Figure 1 also shows one of the two ribs 42 provided with the sidewalls of the chamber 38, which assist in guiding the lower edge of the plate 34 during assembly into the groove 32.

Note that the device is equipped with numerous other apertures in addition to those already described. Thus, the lid 26 has an air hole 44 for holding that portion of the guide 24 which extends beyond the transverse wall 25 at atmospheric pressure. The air hole 44 also serves to allow air to enter chamber 38 after the upper end of the guide 24 has moved below the lower surface 45 of the cover 26 to allow the patient to breathe the drug. The front wall of the jacket 2 is provided with a vent 46 which holds the compartment 6 at atmospheric pressure. This atmospheric pressure 20 is further transmitted by the vent hole 48 to the front surface of the plate 34. This is facilitated by the use of a small longitudinal chamber 50.

t I I t I I '

The device described above works as follows. Let us assume that the device is in the position shown in Figures 1 '«« «1-3, i.e. it is in the tuned position. This is indicated by the fact that • · 25 patients show a green band 10 in the opening 14. The patient inhales • * ... through the mouthpiece, causing the pressure in chamber 38 to fall below t * i * atmospheric pressure. The front surface of the plate 34 is at atmospheric pressure, whereby the differential pressure formed causes the plate 34 to move backward. By holding the top and bottom edges of the plate in the grooves 30 and 32, the result is that the plate · · · \ 30 first enters directly into the space as indicated by line 52. In doing so, it forces the guide 24 slightly upwardly against the spring 28. against. It can be seen that: in the tuned position there is a small opening between the upper end of the guide 24 and the lower surface of the cover 26 to allow this movement. The amount the disk deviates from: \ i in its tuned position from line 52 determines the amount (work) that the disk must perform to access the space directly. Typically, the center of the board has a deviation of a few 1/10 mm. The shorter the distance, the more sensitive the device.

5 The plate then moves past the straight space to a position where it is warped in the opposite direction to the drawing. Once the plate has passed its straight state, it is substantially free of curvature, so that, as it does so, the guide 24 is free to move downward due to the force of the compression spring 28. This causes the body of the aerosol can 8 to move downward, while the discharge arm remains attached to the arm 18, whereby this movement of the body and the arm relative to one another causes a certain dose to be released through the discharge arm and thereby through the outlet 22 and mouthpiece 4. In this case, a red stripe 12 is visible from the opening 14. Note that the spring 28 must be strong enough to overcome the force that would normally chamfer outwardly to the aerosol can 15, power.

Once the patient has received the dose, the device can be returned to its tuned position, and it is desirable that this be done immediately after use. To do this, the patient presses tab 40, which inwardly flexes and forces the plate I i (; 34) back past its straight state to the position shown in the drawings. When this occurs, the guide 24 is forced to move upward, thereby squeezing the spring i «.

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::: 28.

25 ... A second embodiment will now be described, which is represented by Figures 4-7. this

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units of the embodiment which correspond substantially to the units occurring in the first embodiment are referred to by the same reference numerals, however, 100 are added thereto.

«· · * • · ·. · 1 to 30: This second embodiment does not comprise any external spring corresponding to the spring 28 used in the first embodiment, and thus not the guide 24. Instead: it uses a modified aerosol can with a discharge arm 116 instead, to be forced outward by an internal spring (as is customary), 8104051 is forced inwardly. The spring for providing this is schematically shown in Figure 4 where it is represented by reference numeral 154. Thus, in another embodiment, the spring 154 provides the potential energy storage provided by the spring 28 in the first embodiment. , in another embodiment, the body portion of the aerosol can 110 used is elongated to improve its sliding accuracy. A shaft 155 is formed in the shaft member and accommodates a conical seal 156 which is engaged by the discharge arm 116 to prevent it from being moved upward by the action of the pressure spring 154.

10

The groove in which the bottom edge of the flexible plate is located, which groove is designated herein by reference numeral 132, is formed, as in the first embodiment, on the shaft member. However, since in another embodiment there is no guide, the top groove, denoted herein by reference numeral 130, is formed instead by the use of an aerosol can with a uniform plate 157 bent to define the groove 130. The plate 157 has another function, which is to close the top end of the chamber 138 when the device is in the tuned position. To this end, the other end of the plate 157 is curved to form a skate 158 that runs against the rear wall of the chamber 138. Another embodiment is shown in Figures 4-7 in the position it is in when the dose is released, and. . it can be seen that once this position has been reached, the slide 158 has shifted to a position such that it no longer closes the chamber 138 so that air can flow freely through the opening 159 into that chamber.

Another aspect where the second embodiment differs from the first embodiment is the manner in which the device is re-tuned. Instead of the tongue 40 used in the first embodiment, the back wall of the diaper is provided with an opening ... 161, which is covered by an air-impermeable deformable film 160 with edges glued, or otherwise properly secured, to the surrounding portion of the diaper. The device f »» *. 30, the patient then presses the membrane 161, which then contacts the plate i. I. 134, after which the patient continues to press to move the plate past the direct space to contact surface 136.

• 11 «f 1 • 1« · · · «· · * f · • · 9 104051

The third embodiment, shown in Figures 8-10, in many respects resembles the first embodiment, and the corresponding units are denoted by a corresponding number, however, added 200. As in the first embodiment, the third embodiment employs a conventional Aero-5 solder canister part.

It can be seen that in the embodiment of Figures 8 to 10, the resiliently flexible plate, designated herein as 234, is located at the front of the device and not at the rear, as in the first embodiment. The chamber 238 10 is defined between the plate 234 and the front wall 262, and the aperture 263 provides a connection between the mouthpiece 204 and the chamber 238 so that pressure below atmospheric pressure may be exerted on the chamber 238 when inhaled by the user. The mouthpiece is provided with a cover 264 secured to the mouthpiece by a hinge 265 and comprising a support 266 which is the same piece as the cover associated with one end 15 thereof. With the lid closed as in Figures 8-10, the support 266 passes through an opening 167 in the front wall 262 such that the support tip contacts the plate 234 forcing it into contact with the adjacent wall 236. The size of the aperture 167 should be selected such that the airflow through the aperture upon inhalation is at an acceptable level. It is desirable that a little air be allowed in this way so that the inhalation resistance experienced by the patient is not too high. On the other hand, the amount must not be so large that the pressure drop in chamber 238 is insufficient to move plate 234 to the right. Preferably, the device should operate when the patient is inhaled at a rate of about 30 liters / min.

The arms 268 engaging the can 208 are the same piece as the guide 224.

The upper portion of the aerosol can body is surrounded by a tube 269, and a spring 228 is compressed between the tube 269 and the arms 268 to force the can body down.

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8 to 9, the guide 224, and thus the body of the can - 30208, cannot move due to the spring 228 due to the presence of the plate 234.

«· · ·

When the patient wishes to use the device, he opens the lid 264, whereupon the support 266 moves • · ·. · '··. disc 234 is in position as shown until the patient inhales through the mouthpiece 204, whereupon the vacuum created in chamber 238 causes the plate 234 to bend to the right, allowing the guide 224 to move downwardly, moving the can body 268 according to them. The patient thus receives a dose of the drug. After use, the patient again closes the cover 264, whereupon the support 266 pushes the plate 234 back to the position shown in the drawings, and the device is again tuned for the next use.

5

The side walls of chamber 238 are provided with a pair of ducts 270 to facilitate air intake by the patient during inhalation.

The three embodiments described so far operate automatically in the sense that the inhalation function itself releases the dose.

The fourth embodiment, shown in Figures 11-14, is manual, with the inhalation function allowing for dose release, but not per se. The units according to this embodiment, which generally correspond to the units of the first embodiment, are designated by the same reference numerals, however, 300 are added thereto.

In a fourth embodiment, the relative motion between the aerosol can body and the discharge arm is manually generated by the patient. To accomplish this, the patient presses the guide 324 inwardly with respect to the diaper 302, whereby to facilitate the patient 20 to hold the device therein, the diaper is provided with a depression 372 adjacent the stem member. However, unless the patient inhales, "as he attempts to manually operate the device, there can be no relative movement between the controller 324 and the diaper 302 because plate 334 is present.

In this embodiment, in contrast to the previous embodiments, the plate is in the 25 plane with the device in its tuned position and to ensure that: the disk remains in the correct position when the device is tuned, it is pre-warped so that its natural tendency 11 and 13. The plate is rotated to be prevented by walls 336, whereby the plate is pressed against these walls by a force dependent on the degree of curvature * • 30 used. To facilitate mounting of the plate 334, ribs 373 and IM · 374 are formed on the inner surface of the sheath 302 and the guide 324.

* «· I I ·

As the patient inhales, the front of the plate 334 is subjected to a pressure lower than atmospheric pressure, causing the plate 334 to turn to the right, which may result in manual force exerted on the skate 324 inward relative to the shell 302. This is shown in Figure 14. As the center portion of plate 334 passes past ribs 375 formed on the inner surface of guide 324, air can flow freely into the mouthpiece 304 through vent 348 and into longitudinal 5 chamber 350 and longitudinal edges of plate 335.

After use, the unit will automatically re-arm. This is because, when the patient stops pressing the guide 324, the aerosol can body body is able to return to its original position by the force of the spring of the aerosol valve. This moves the controller 324 back to its original position. At the same time, the energy stored in the disk 334 promotes the controller returning to its original position.

The embodiment just described, although having the advantage of simplicity, has the disadvantage that its use requires a certain degree of convenience from the user. This is especially so because the user must be able to correctly estimate the amount of force they are using. If the force is too weak, the device will not work at all, while excessive force may damage the device. To reduce this problem, the embodiment just described may be modified by providing it with a mechanism that limits the force that can be transmitted by the user to the device. This fifth embodiment is shown in Figures 15-17. With the exception of the transmission mechanism, the units of the fifth embodiment substantially correspond to the fourth embodiment. form units, and those units of the fifth embodiment which generally correspond to units of the fourth embodiment are designated by the same reference numerals, but with a further 100 added.

• · · m · ·

In the embodiment shown in Figs. 15-17a, the upper surface of the controller 424 is * · *: provided with a bracket 480 to which a resilient key 481 is mounted. The force exerted by the user · · v through the spring is transmitted to the controller 30 424 and Presence of 482 which hits ribs 483 vertically at the top of diaper 402 when user exerts sufficient force on front face 484 of key 481. In the illustrated embodiment, key 481 is formed of strip spring steel as shown in FIG. parts, for example, a helical spring having an extended head to form a physical barrier.

Using the resilient key in the embodiment of FIGS. 15-17a not only avoids the need for the user to correctly assess the level of force she is using, but also facilitates the necessary coordination. Thus, the user can press the key 481 until it no longer goes down, thereby reserving energy for the resilient key, after which, when ready, he can inhale. When inhaling-10, the force stored on the key then forces the controller down, which then releases the dose.

The sixth embodiment, shown in Figs. 18-22, is an alternative modification of the fourth embodiment, whereby the purpose of the modification this time is to make the device function automatically by providing it with an energy storage device. The units of the sixth embodiment, which correspond generally to those of the fourth embodiment, are denoted by the same reference numerals, but with a further 200 added.

The device shown in Figures 18-22 is provided with a mouthpiece cover 586 which:. 18, fits the mouthpiece 504. The lid 586 comprises a tubular inner sleeve 587, the end of which is located in the mouthpiece. i .: 504. An energy storage device in the form of a spiral spring 588 is mounted on the sleeve 587.

·: ··: 25 tM

v: The cover 586 is provided with a pair of pins 589, the upper end of the sheath 502 being provided with a puncture portion 590 comprising grooves 591 to which the pins 589 respectively fit to allow the cover to be positioned at the upper end of the device.

· »· V: Figures 21 and 22 show cover 586 so set. When the cover 586: 30 is placed on the puncture portion 590, the helical spring 588 is compressed in the longitudinal direction, resulting in a spring force exerted downward on the guide 524 as spring. · · ·. thus performs a function comparable to springs 28 and 228 in the first and third embodiments, respectively.

• · · 13 104051 Thus, to operate the device, the patient removes the cover 586 and inserts it into the pin portion 590 to tune the device. The patient then inhales to receive a dose of the drug, after which he removes the lid from the 586 sting. Thereby, both the guide 524 and thus the aerosol can body 508 may return to their original positions. The lid 586 can then be re-placed on the mouthpiece 504.

As already mentioned, sheets 34,134, 234, 334, 434 and 534 can be made of a resiliently flexible metal such as steel. However, other materials such as plastics and metal / plastic laminates may be used instead. The springs used in the various embodiments are normally metallic, and the remainder, with the exception of the aerosol can itself, is most conveniently made of a plastic material to be molded. All the aerosol cans used, including the unusual cans used in the second embodiment, are of the type 15 having a measuring chamber which is automatically refilled with a dose of liquid as the discharge arm moves outwardly relative to the can body.

I <· • • * • • • • * * • • * • »« · ** • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • · · • * f «·

Claims (16)

An inhalation device for use with an aerosol can (8) comprising a body and a discharge spindle (16) movable relative to the body from a 5 resting position prevented from being discharged to an operating position comprising a housing (2,102,202), 302, 402, 502) for the inhaler, an outlet (4,104, 204, 304,404, 504) in the body through which the patient can inhale, and an inhibitory and pressure-sensitive member having a first position for preventing relative movement between the discharge spindle and body 10. and a second position in which it permits such movement, wherein said member recognizes the reduced pressure produced by inhalation of the patient and in response moves from the first position to the second position, characterized in that said blocking and pressure-responsive member is resiliently flexible plate (34, 134,234, 334,434; 534) extending from a first position of 15 pes than the fixed relative to, and a second position relative to the frame of the spray-fixed portion, wherein the plate is bent when moving from the first position to the second position or vice versa. Device according to Claim 1, characterized in that it comprises an energy store which can be used - by moving the blocking and pressure-sensitive member to its second position - to move said body and the discharge spindle relative to each other in said operating position. I I 't I · Ml Device according to claim 2, characterized in that said energy storage is a spring (28, 154, 228, 588). m * • «· Device according to Claim 3, characterized in that the discharge spindle (16, '* / 216) rests on a spindle support (18, 218) which is fixed with respect to the housing (2, 102), and said body is longitudinally oriented movable in the housing to move the body and disengage • f I 30 the spindle into and out of said operating position, and the spring (28, II ·: 228) is a spring forcing the housing toward the operating position. A device according to claim 4, characterized in that said body member is mounted on the guide member (24, 224) movable relative thereto, and said spring 15 104051 (28, 228) acts on the guide member and the housing or nesting star. between the fixed member (269). Device according to Claim 4 or 5, characterized in that the spring (588) 5 is provided with a means (589) by means of which the spring can be removably mounted in a position where it forces the housing towards the operating position. Device according to Claim 6, characterized in that the spring (588) is located in a cover member (586) adapted to act as a cover for the inhalation opening (504) 10 when the spring and the cover member are removed from the aforesaid position Device according to Claim 3, characterized in that the discharge spindle (116) rests on a fixed spindle support relative to the housing (102), the body portion Liu-15 extending longitudinally in the housing to bring the body and the discharge spindle into and out of operating position. located in said frame member and disposed obliquely with respect to the frame member and discharge spindle towards the operating position, and the device further comprises means (156) for holding the discharge spindle (116) in the strut against the inclined force of the spring (154). 20 Device according to Claim 2, characterized in that the energy reserve is in the form of a spring-loaded hand-operated actuator (481), which actuator is disposed to contact the housing (402) when a force is applied to it, a specified maximum to prevent application of a force exceeding said maximum 25 between said body and said discharge spindle. * · · V · · Device according to Claim 1, characterized in that the plate (34, 134, · · · '234) deflects in one direction when in its first position and in the opposite direction: · 30: in the second position, whereby the plate bypasses it. - an intermediate space in the salt when moving from one position to another. • · · • · Device according to Claim 1, characterized in that the plate (334, 434, 534) is substantially plane when in its first position and deflected in its second position, wherein the plate has a natural curvature opposite to the direction in which it bends in its second position, and there is a device available to prevent the disc from being in its first position to assume its natural curvature. 5 Device according to Claim 1, characterized in that it comprises a tuning device for returning the plate (34,134, 234, 334, 434, 534) to its first position. Device according to Claim 12, characterized in that the tuning device comprises a tuning member (40,161, 266) which can be moved by the user in contact with the resilient plate (34,134, 234), forcing it into its first position. Device according to Claim 13, characterized in that the tuning member is an elastically flexible tongue (40) forming part of the housing wall. 14 104051 Device according to Claim 14, characterized in that the tuning member is an elastically flexible film (161) forming part of the housing wall. 20 Apparatus according to claim 13, characterized in that the inlet is provided with a lid (264) on which the tuning member (266) is located, wherein an opening (267) is provided in the wall of the housing (202) through which the tuning member can pass. '··· * flexible plate (234) with inlet closed with lid. 25 • • • • • • • • I I • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • I • · I · • »·« · III • · · • · 17 104051